Androgenic regulation of hepatic gene expression

Androgen-dependent synthesis of α2u globulin in the rat liver has been used in our laboratory as a model for studying the effect of sex hormones on hepatic gene expression, α2u Globulin is a group of low molecular weight (M_r ∼18,000) male specific urinary proteins synthesized and secreted by hepatocytes. In the male rat hepatic synthesis of α2u globulin begins at puberty (∼40 days), reaches a peak level (∼20 mg/day) at about 75 days and declines during old age. Androgens can induce α2u globulin in ovariectomized female rats in vivo and in the liver perfusion system in vitro. However, both prepubertal and senescent (≫800days) male rats not only do not produce α2u globulin but are also refractory to androgen administration, α2u Globulin is coded by a multigene family comprising about 20-30 gene copies per haploid genome. All of these gene copies seem to express translationally active mRNAs giving rise to individual isofonns of α2u globulin. Appearance and disappearance of the cytoplasmic androgen-binding protein (CAB) correlates with the androgen responsiveness of hepatocytes. Photoaffinity labeling of the hepatic cytosol shows that the biologically active binding protein, found in the cytosol of the mature male rat liver, has a molecular weight of 31 kDa. A molecular transition of the 31-kDa CAB to a biologically inactive 29-kDa form may be the basis of hepatic androgen insensitivity during prepuberty and senescence.